Without limiting the scope of the invention, its background is described in connection with the delivery of active agents in vivo.
It is well known that low-molecular weight pharmaceutics are rapidly cleared from circulation following intravenous injection. This restricts the amount of time a therapeutically relevant dose can be maintained and greatly limits the effectiveness of many of these compounds. A great deal of research has been conducted in an effort to prolong plasma residence times via conjugation to macromolecular constructs that display extended circulation profiles, such as polymers or proteins. However, these methods require the conjugation to be carried out ex vivo.
One such method is taught in U.S. Pat. No. 7,344,698, issued to Lanza, et al., for Integrin targeted imaging agents. Briefly, this patent teaches emulsions of nanoparticles formed from high boiling liquid perfluorochemical substances, wherein the particles are coated with a lipid/surfactant coating are made specific to regions of activated endothelial cells by coupling said nanoparticles to a ligand specific for αvβ3 integrin, other than an antibody. The nanoparticles may further include biologically active agents, radionuclides, or other imaging agents.
Yet another example is U.S. Pat. No. 6,818,630, issued to Duncan, et al., for biologically active materials, particularly materials that comprise a biodegradeable polymer, linked to a biologically active agent. The patent is said to teach materials known as polymer-drug conjugates that typically contain a therapeutic agent, for instance a bioactive cytotoxic drug linked to a polymer backbone (the linkage is typically a convalent linkage). In some embodiments the disclosure concerns other polymer conjugates including those where the biologically active agent is an imaging agent, such as a tyrosinamide, a diagnostic agent, or a targeting agent, such as biotin.
Yet another example is U.S. Pat. No. 5,965,131, issued to Griffiths, et al., for the delivery of diagnostic and therapeutic agents to a target site. Briefly, this patent teaches improved in vivo pretargeting methods for delivering diagnostic or therapeutic agents to a target site in a mammal uses a clearing agent that binds to the target-binding site of the targeting species, whereby non-bound primary targeting species is cleared from circulation but the clearing agent does not remove the bound primary targeting species. Anti-idiotype antibodies and antibody fragments are preferred clearing agents. Fast clearance is achieved by glycosylating the clearing agent with sugar residues that bind to the hepatic asialoglycoprotein receptor.